miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis.
Inflamm Bowel Dis
; 21(9): 2039-51, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26083618
ABSTRACT
BACKGROUND:
Longstanding ulcerative colitis (UC) bears a high risk for development of UC-associated colorectal carcinoma (UCC). The inflammatory microenvironment influences microRNA expression, which in turn deregulates target gene expression. microRNA-26b (miR-26b) was shown to be instrumental in normal tissue growth and differentiation. Thus, we aimed to investigate the impact of miR-26b in inflammation-associated colorectal carcinogenesis.METHODS:
Two different cohorts of patients were investigated. In the retrospective group, a tissue microarray with 38 samples from 17 UC/UCC patients was used for miR-26b in situ hybridization and quantitative reverse transcription polymerase chain reaction analyses. In the prospective group, we investigated miR-26b expression in 25 fresh-frozen colon biopsies and corresponding serum samples of 6 UC and 15 non-UC patients, respectively. In silico analysis, Ago2-RNA immunoprecipitation, luciferase reporter assay, quantitative reverse transcription polymerase chain reaction examination, and miR-26b mimic overexpression were employed for target validation.RESULTS:
miR-26b expression was shown to be upregulated with disease progression in tissues and serum of UC and UCC patients. Using miR-26b and Ki-67 expression levels, an UCC was predicted with high accuracy. We identified 4 novel miR-26b targets (DIP1, MDM2, CREBBP, BRCA1). Among them, the downregulation of the E3 ubiquitin ligase DIP1 was closely related to death-associated protein kinase stabilization along the normal mucosa-UC-UCC sequence. In silico functional pathway analysis revealed that the common cellular pathways affected by miR-26b are highly related to cancerogenesis and the development of gastrointestinal diseases.CONCLUSIONS:
We suggest that miR-26b could serve as a biomarker for inflammation-associated processes in the gastrointestinal system. Because miR-26b expression is downregulated in sporadic colon cancer, it could discriminate between UCC and the sporadic cancer type.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
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Colitis Ulcerosa
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Biomarcadores de Tumor
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MicroARNs
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Carcinogénesis
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Inflamm Bowel Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2015
Tipo del documento:
Article